Background: Valproic acid (VPA) is a broad spectrum antiepileptic drug (AED) that is generally regarded
as a first-choice agent for most forms of idiopathic and symptomatic generalised epilepsies. Available data
suggest that menstrual disorders and certain endocrine manifestations of reproductive system disorders may be
more common in women treated with VPA than in those treated with other AEDs.
Methods: A PubMed search for MEDLINE was undertaken to look for studies using the terms “VPA metabolism”,
“VPA and sexual functions in men”, “VPA and sexual functions in women” and “VPA metabolism and endocrine
disorders” as key words. The period covered was approximately 20 years.
Results: In women, VPA medication is associated with hyperandrogenism, polycystic ovary/polycystic ovarian syndrome, menstrual disorders
and ovulatory failure. Men on VPA therapy show abnormalities in androgens blood levels, sperm motility and erectile dysfunctions.
VPA negatively affects the release of luteinizing hormone, follicle stimulating hormone and prolactin but also the drug interferes in
peripheral endocrine hormones. Its broad inhibitory action on cytochrome and glucuronidation systems can lead to high serum concentration
of testosterone, androstenedione and dehydroepiandrosterone sulfate. VPA-dependent obesity and hyperinsulinemia can further contribute
to an increase in sexual dysfunctions.
Conclusions: VPA interferes with the endocrine system at multiples levels causing several reproductive and sexual dysfunctions in
women and men with epilepsy, especially when administered in pubertal age. Since VPA is a first line AED both in children and adult
with epilepsy and long-term medication with this drug is sometimes necessary, it is very important for physicians to implement strict
monitoring of patients taking VPA in order to identify these kinds of side effects at an early stage.